Mass spectrometry (MS) is a well-known technique for obtaining a molecular weight and structural information on chemical compounds. According to mass spectrometry, molecules may be “weighed” by ionizing the molecules and measuring the response of their trajectories in a vacuum to electric and magnetic fields. Ions are “weighed” according to their mass-to-charge (m/z) values.
Atmospheric pressure ion sources (API) have become increasingly important as a means for generating ions used in mass spectrometers. Some common atmospheric pressure ion sources include Electrospray or nebulization assisted Electrospray (ES), Atmospheric Pressure Chemical Ionization (APCI), and Matrix Assisted Laser Desorption Ionization (MALDI). These ion sources produce charged particles, such as protonated molecular ions or adduct, from analyte species in solution or solid form, in a region which is approximately at atmospheric pressure.
Conventionally a single type source is used one at a time. However, it is sometimes preferable to use multiple ion sources simultaneously, for example to increase the number of samples analyzed per unit time, also know as throughput. Also, some analyte samples respond well to one approach, such as ESI, and others to another approach such as APCI, and it is desirable to provide a simultaneous approach that is optimal for the formation of charged species.
Mass spectrometers generally operate in a vacuum maintained between 10−4 to 10−10 torr depending on the mass analyzer type. Thus once created, the charged particles must be transported into vacuum for mass analysis. A portion of the ions created in the API sources are entrained in the bath gas within the API source chamber and are swept into vacuum along with a carrier gas through an orifice into vacuum. One challenging aspect for high sensitivity lies in efficient transportation of the desired charged ions from atmosphere to the vacuum.
The API sources are advantageous because they provide a gentle means for charging molecules without inducing fragmentation. They also provide ease of use because the sample can be introduced at atmosphere.
API sources have a disadvantage of producing high chemical background and relatively low sensitivity. This is believed to be caused by sampling of impurities attached to the analyte ion (for example, cluster molecules, atoms or ions, or other undesired adduct ions), caused by incomplete desolvation during the API process. In this way, along with desolvated ions, many such droplets of varying diameters can enter into the mass spectrometer and consequently produce a large level of chemical noise across the entire mass range. Additionally incompletely vaporized droplets linger near the sampling orifice.
These problems can be most severe for high liquid sample flow rates, that typically range from 0.2 to 2.0 mL/min. Efficient Electrospray Ionization (ESI) at high flow rate requires sufficient heat for desolvation and a method to deter large clusters from entering the vacuum chamber while enhancing the ion capture. High flow rate analyses are important to industries that have large throughput requirements (such as drug development today, and in the future, protein analysis) because such flow rates are presently necessary for the High pressure Liquid Chromotography (HPLC) techniques performed prior to mass spectrometric analysis. For most modern applications of ESI and APCI, liquid samples are passed through the source at high flow rates.
To reduce the problem of incomplete desolvation, heated gases are commonly employed to vaporize with a flow direction opposite, or counter, to sprayed droplets in order to desolvate ions at atmospheric pressure. Since the heated gases remove much of the solvent vapor from the stream of gas before being drawn into the vacuum chamber, this technique increases the concentration of ions of interest in the vacuum chamber.
For example, U.S. Pat. No. 4,023,398 teaches a technique whereby ions pass through an orifice into a vacuum chamber, while a gas curtain upstream from the orifice reduces transmission of solvent vapor into the vacuum chamber. The gas is heated to hasten evaporation of the solvent from the droplets, thereby producing desolvated ions at substantially atmospheric pressure. U.S. Pat. No. 4,531,056 teaches a similar technique, whereby an inert gas is introduced into the electrospray chamber in a direction opposite to a flow from the capillary. The electrospray chamber remains at or slightly greater than atmospheric pressure. Ions of interest are produced within the electrospray chamber, and the inert gas flow substantially reduces the concentration of solvent vapor that enters the analyzer. U.S. Pat. Nos. 4,842,701 and 4,885,076 disclose a system that combines capillary zone electrophoresis with electrospray for gas analysis of an analyte mixture. Again, the electrospray occurs at atmospheric pressure, and a heated countercurrent gas flow technique is used to desolvate the spray droplets.
While the counter flowing gas concept described above results in reasonable sensitivity, it is typically incorporated using a largely coaxial geometry between the sprayer and the mass spectrometer. This substantially decreases the ruggedness of the interface between the electrospray and the mass spectrometer, since a portion of the spray can still enter the mass spectrometer. It also reduces the sensitivity since the desolvation time spent in the flow is small.
Now, importantly, it is often useful and desirable to operate with multiple ion sources substantially simultaneously, for example using two or more ESI sources, or an APCI and ESI source, while also reducing the chemical noise and maintaining the simplicity of the atmospheric pressure source. This permits higher throughput or sensitivity (improved signal-to-noise) of sample than is possible with a single ion source, as well as other useful functions such as providing the possibility of on-the-fly calibration. Thus signal-to-noise (sensitivity) and functionality are enhanced,
Prior art interfaces exist that contain multiple sprayers. However they are complex devices, requiring moving parts such as rotating cylinders and blocking apertures to select the appropriate sprayer, or utilizing multiple apertures to a vacuum system, thereby increasing vacuum load, increasing cost or reducing sensitivity. For example, U.S. Pat. No. 6,784,422 teaches approaches for multiple sprayers using multiple sampling apertures directed into the low pressure of the mass spectrometer. It also teaches various approaches to blocking these apertures, and switching the ion beams near these apertures. This approach disadvantageously increases vacuum load, increasing cost or reducing sensitivity.
It is therefore desirable to provide an improved mass spectrometer interface for atmospheric pressure ionization sources suitable for multiple sources having improved sensitivity, enhanced stability and ruggedness and more functionality than prior interfaces, with substantially reduced complexity and cost, and reduced or eliminated source-to-source interference.